title: Neurological manifestations in patients with Gaucher disease and their relatives, it is just a coincidence?
abstract: Gaucher disease (GD) is an autosomal recessive disorder characterized by defective function of glucocerebrosidase. GD presents a wide spectrum of manifestations, and patients and their relatives may develop neurological abnormalities more frequently than the general population. This study aims to determine the presence of neurological symptoms (NS) and Parkinson's disease (PD) in Spanish GD patients and their relatives. We surveyed 87 GD Spanish families and validated the information obtained on the neurological involvement through their physicians, as well as the historical data included in the Spanish Gaucher Disease Registry. Neurological abnormalities were correlated with the genetic characteristics. Statistical analyses included descriptive parameters, ANOVA, t-test, correlation study and Pearson coefficient. Information was obtained from 118 patients and 324 relatives. Out of 110 patients with type 1 GD, 32 (29.1%) reported NS and 7 (6.4%) had PD. In relatives, a total of 39 (13.1%) subjects had NS, including 16 with PD (5.3%). The prevalence of NS in genetic carriers (15.9%) was greater than that in non-carriers (5.9%; p < 0.01). Patients with PD carried the following GBA mutations: S364R, D409H, L444P, R257Q, IVS4-2A > G, c.500insT, and L336P. Relatives with PD exhibited a wide spectrum of mutations: L444P, N370S, V398I, R257Q, G202R, c.1439-1445del7, [E326K; N188S], and c.953delT. We observed a high incidence of PD in type 1 GD and relative's carriers. PD was more frequent in carriers of L444P and other rare GBA mutations. Therefore, it is important to perform a systematic neurological exam in patients with type 1 GD and carriers with high risk mutations.
authors.affiliation: Hematology Department, Miguel Servet University Hospital, Pº Isabel La Católica 1-3, 50009 Zaragoza, Spain. giraldo.p@gmail.com
authors.forename: Pilar
authors.initials: P
authors.lastname: Giraldo
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Capablo
authors.forename: Pilar
authors.initials: P
authors.lastname: Alfonso
authors.forename: Beatriz
authors.initials: B
authors.lastname: Garcia-Rodriguez
authors.forename: Paz
authors.initials: P
authors.lastname: Latre
authors.forename: Pilar
authors.initials: P
authors.lastname: Irun
authors.forename: Alicia Saenz
authors.initials: AS
authors.lastname: de Cabezon
authors.forename: Miguel
authors.initials: M
authors.lastname: Pocovi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D005776:Gaucher Disease / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D006306:Health Surveys; D006801:Humans; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D015995:Prevalence; D055815:Young Adult